Cocaine is a highly addictive substance of abuse and its use maintains the drug-taking habit by directly affecting the reward pathways. Cocaine use can have detrimental physical and emotional consequences. Regardless of the frequency of use cocaine users can experience heart attacks or strokes. Cocaine abusers can also subject to experiencing anxiety, depression, or paranoia. Currently there are no small molecule drugs that can block the addictive or toxic effects of cocaine. However, it has been shown that an enzyme called cocaine esterase (CocE) can accelerate the breakdown of circulating cocaine or reduce its effects. Bacterial CocE has been found to be easily expressed or purified (Kcat=7.8 s−1 Km=<1 μM). Administration of a cocaine esterase (CocE) can decrease the half-life of cocaine in both the brain or plasma. A major hurdle with using CocE as a therapeutic is that it can be unstable and can be quickly degraded.
A strategy to antagonize the negative effects of cocaine has been to increase its metabolism by using cocaine-specific enzymes, such as cocaine esterase (CocE). The use of cocaine specific enzymes have shown to decrease the half-life of cocaine in both the plasma and in the brain. But a limitation is that CocE can be unstable in vivo and can have a very low half-life.